S181. THE STATE OR TRAIT COMPONENT OF DOPAMINE AND GLUTAMATE DYSFUNCTION IN THE RISK FOR PSYCHOSIS: AN IN VIVO MULTIMODAL IMAGING STUDY OF INDIVIDUALS WITH 22Q11.2 DELETION

Abstract

Background: Advances in in vivo imaging studies have provided further evidence of dopaminergic and glutamatergic dysregulation in schizophrenia. Despite this, the degree to which these alterations are trait markers linked to genetic risk for psychosis or reflects state changes is not clear from previous studies. Individuals with 22q11.2 deletion have 30 -fold increase for developing psychosis. The aims of our study were to investigate dopaminergic and glutamatergic function in individuals with 22q11.2 deletion. Methods: 21 antipsychotic naive individuals with 22q11 deletion and 26 healthy volunteers received 18F DOPA PET. A Patlak analysis was applied to calculate influx constants (Ki values) for the whole striatal ROI relative to uptake in the cerebellar reference region. 17 individuals with 22q11.2 deletion and 30 healthy controls had MRS. Voxels were placed on the anterior cingulate cortex and left striatum. Spectra were analyzed using LC Model version 6.3-1L. Results: DSC in the whole striatum was significantly increased in the individuals with 22q11 deletion compared to healthy controls (Cohen's d= 1.47, p< 0.000). No difference was found between groups in Glx levels in anterior cingulate cortex and left striatum (p=0.29; p=0.86, respectively). Psychopathology scales were not correlated with either dopaminergic or glutamatergic function in the group of 22q11. Conclusions: Our findings provide evidence that DSC has a strong trait component and glutamatergic dysfunction may be most likely associated with disease status. Future studies with longitudinal design are warranted to further investigate the role of dopamine and glutamate in individuals with 22q11.2 deletion.